Epoxide-hydrolase-initiated hydrolysis/rearrangement cascade of a methylene-interrupted bis-epoxide yields chiral THF moieties without involvement of a "Cyclase"

Barbara T. Ueberbacher, Gustav Oberdorfer, Karl Gruber, Kurt Faber

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In contrast with electrophilic enzyme-catalysed cyclisations in terpenoid biosynthesis, cyclisations of tetrahydrofuran moieties found in several groups of natural products, such as annonaceous acetogenins, neurofurans and phytooxylipins, appear to proceed through a nucleophilic cascade mechanism starting from bis-epoxy fatty acid precursors. This hypothesis was verified by epoxide-hydrolase-catalysed hydrolytic ring-opening/cyclisation cascades starting from a methylene-interrupted meso-bis-epoxide model substrate, which furnished the corresponding THF products with excellent de and ee values. Molecular modelling showed that the points of enzyme attack were consistent with the stereospecificities of the enzymes, whereas the stereochemical courses of the cyclisation were solely governed by Baldwin's rules and did not invoke the involvements of a "cyclase".

Original languageEnglish
Pages (from-to)1697-1704
Number of pages8
JournalChemBioChem
Volume10
Issue number10
DOIs
Publication statusPublished - 6 Jul 2009

Fingerprint

Epoxide Hydrolases
Cyclization
Epoxy Compounds
Hydrolysis
Enzymes
Acetogenins
Molecular modeling
Biosynthesis
Terpenes
Biological Products
Fatty Acids
Substrates

Keywords

  • Bis-epoxides
  • Cascade reactions
  • Enzyme models
  • Epoxide hydrolases
  • Hydrolases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Epoxide-hydrolase-initiated hydrolysis/rearrangement cascade of a methylene-interrupted bis-epoxide yields chiral THF moieties without involvement of a "Cyclase". / Ueberbacher, Barbara T.; Oberdorfer, Gustav; Gruber, Karl; Faber, Kurt.

In: ChemBioChem, Vol. 10, No. 10, 06.07.2009, p. 1697-1704.

Research output: Contribution to journalArticleResearchpeer-review

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